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Updated: May 17, 2026
Assays for Validating Histone Acetyltransferase Inhibitors
Published on: August 6, 2020
Histone deacetylases expression in atypical teratoid rhabdoid tumors
Simone Treiger Sredni1, Abby L Halpern, Christopher A Hamm
1Division of Pediatric Neurosurgery, Ann and Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Avenue, Box # 28, Chicago, IL 60611, USA. ssredni@northwestern.edu
Purpose:
Atypical teratoid rhabdoid tumors (ATRTs) are rare, highly malignant central nervous system tumors that occur during infancy and early childhood. Their poor outcome and resistance to conventional chemotherapies and radiotherapy, urges the development of new therapies. Recent studies have evaluated the effects of histone deacetylase inhibitors (HDACi) as a new potential treatment for ATRTs. However, most HDACi act unselectively against all, or at least several, histone deacetylase (HDAC) family members. We hypothesized that specific HDAC family members are deregulated in ATRT and therefore a more selective class of HDACi would be beneficial to patients with ATRT.
Methods:
To test our hypothesis, we evaluated the expression level of different HDAC family members in ATRTs. Eight ATRTs were compared to six medulloblastoma samples in regards to the level of expression of the 18 HDAC family members as determined by microarray gene expression profiling.
Results:
HDAC1 was the only member of the HDAC family to be significantly differentially expressed in ATRTs (FC = 4.728; p value = 0.00003).
Conclusions:
A class of HDACi specifically targeting HDAC1 may allow for the desired therapeutic benefits with fewer side effects for children with ATRT.
Insights
Atypical teratoid rhabdoid tumors (ATRTs) are aggressive childhood brain cancers. Targeting histone deacetylase 1 (HDAC1) may offer a more effective and safer treatment for ATRTs.
Area of Science:
- Neuro-oncology
- Molecular biology
- Cancer genetics
Background:
- Atypical teratoid rhabdoid tumors (ATRTs) are rare, aggressive central nervous system cancers in infants and young children.
- Current treatments for ATRTs have limited efficacy due to tumor resistance.
- Histone deacetylase inhibitors (HDACi) are being investigated, but broad-acting inhibitors may cause side effects.
Purpose of the Study:
- To investigate the expression of histone deacetylase (HDAC) family members in ATRTs.
- To identify specific HDACs that are deregulated in ATRTs.
- To explore the potential of targeted HDAC inhibitors for ATRT therapy.
Main Methods:
- Microarray gene expression profiling was used to compare HDAC family member expression.
- Expression levels of 18 HDAC members were analyzed in eight ATRT samples.
- ATRT samples were compared against six medulloblastoma samples.
Main Results:
- Histone deacetylase 1 (HDAC1) was significantly overexpressed in ATRTs compared to medulloblastomas.
- The differential expression of HDAC1 showed a fold change of 4.728 (p=0.00003).
- HDAC1 was the sole significantly differentially expressed HDAC family member identified.
Conclusions:
- HDAC1 is a key deregulated target in atypical teratoid rhabdoid tumors.
- Developing HDAC inhibitors that specifically target HDAC1 could be a promising therapeutic strategy.
- Targeted HDAC1 inhibition may improve treatment outcomes and reduce side effects for children with ATRT.
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